Nrg Oncology/Rtog 0529: Long-Term Outcomes Of Dose-Painted Intensity Modulated Radiation Therapy, 5-Fluorouracil, And Mitomycin-C In Anal Canal Cancer

This phase II trial demonstrated the utility of DP-IMRT in reducing the acute toxicity of 5FU/MMC chemoradiation for anal cancer. This is the report of the secondary endpoints estimating long-term efficacy and evaluating late effects. Patients with T2-4N0-3M0 anal cancer received 5FU/MMC days 1 and 29 of DP-IMRT, prescribed per stage - T2N0: 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3: 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. Disease-free survival (DFS), colostomy-free survival (CFS) and overall survival (OS) were estimated with Kaplan-Meier, and local-regional failure (LRF), colostomy failure (CF) and distant failure (DF) with cumulative incidence methods. Univariate Cox proportional hazards models were used to identify the impact of gender, tumor diameter [<4 vs. ≥4 cm], and T, N and overall stage on DFS/OS, with Fine-Gray regression models used for LRF/DF. Late adverse events (>90 days from the start of treatment) were graded with CTCAE v3.0. Sixty-three patients accrued, with 52 evaluable. AJCC sixth edition stage included: 54% II, 25% IIIA, and 21% IIIB. Median f/u is 7.9 years (0.02-9.2), compared to 6.1 years (0.05-11.8) for the MMC arm of RTOG 9811 (65% II, 15% IIIA, 16% IIIB, 4% unknown). Five and eight year efficacy outcomes are shown in Table 1. On 0529 univariate analysis, female gender significantly predicted for decreased LRF (HR = 0.13, 95% CI = 0.03-0.54; P = 0.0048) and improved OS (HR = 0.33, 95% CI = 0.12-0.91; P = 0.032); tumor size >4 cm was associated with increased LRF (HR = 3.78, 95% CI = 0.78-18.40; P = 0.099) and poorer OS (HR = 2.41, 95% CI = 0.87-6.65; P = 0.089). Worst overall 0529 late effects included: 18% grade 1, 55% grade 2, 16% grade 3, 0% grade 4, 2% grade 5 (sinus bradycardia), and two possibly associated second primaries (myelodysplasia, prostate). Nine thousand eight hundred eleven displayed similar grade 3+ profiles, however, was scored using the RTOG/EORTC Late Radiation Morbidity Schema. Further analysis of 0529 recurrence patterns and late effects will be provided at the annual meeting. Chemoradiation using DP-IMRT for anal canal cancer provided reduced acute morbidity with comparable long-term efficacy and late effects as compared to non-conformal radiation delivery.Tabled 1Abstract 138; Table 10529(n = 52)9811 MMC Arm(n = 325)EndpointTotalEvents5y-%(95% C.I.)8y-%(95% C.I.)TotalEvents5y-%(95% C.I.)8y-%(95% C.I.)LRF816 (7, 27)16 (7, 27)6720 (16, 25)22 (17, 27)CF610 (4, 20)12 (5, 23)3812 (9, 16)12 (9, 16)DF1116 (7, 27)22 (12, 34)4613 (10, 17)16 (12, 21)DFS2068 (53, 79)60 (45, 72)12268 (62, 73)57 (50, 63)CFS1774 (59, 84)66 (51, 77)10672 (67, 77)63 (57, 69)OS1676 (61, 86)68 (53, 79)8778 (73, 83)69 (62, 74) Open table in a new tab